Telomere and telomerase are a key factors that regulate cell replicative lifespan. Telomere shortening has been observed in many types of cells in vitro and in cross-sectional analyses, and significantly shortened telomeres induce cell senescence and apoptosis. However, it remains to be determined how telomere length change in vivo and whether shortened telomeres contribute to age-associated decline of function. Telomerase is an enzyme that synthesizes telomere and is highly regulated in lymphocyte activation. To understand the in vivo change of telomere length and telomerase activity, we are conducting a longitudinal analysis of 1) telomere length of peripheral blood lymphocytes (T and B cells) and monocytes and 2) telomerase expression in peripheral blood T and B cells (at rest and after activation) of approximately 200 individuals (starting age from 20s to 90s). We found that telomere changes in vivo over five year time were quite dynamic: shortening in approximately 30%, no obvious change in 60%, and increase in 10% of the participants. We also observed a decrease of telomerase activity in T and B cells with age. Together, these findings demonstrated for the first time that the rates of telomere attrition in blood lymphocytes and monocytes in vivo were highly dynamic, not only shortening but also lengthening were observed. In addition, we observed telomerase activity decreases with age in lymphocytes, however, its physiological significance requires further study. Currently, we are conducting cross analysis of changes of telomere length and telomerase activity in vivo with lymphocyte composition and health conditions as well as assessing the role of telomere length in the overall immune function.